Tissue Healing Process Research Articles

A novel method to detect carotid artery in-stent restenosis.

Carotid artery stenosis is a major risk factor for ischemic stroke. Despite carotid artery stenting, in-stent restenosis (ISR) remains challenging. Pigs serve as an ideal ISR model. This study aims to establish a novel porcine model of carotid ISR using open-loop and closed-loop stents and to assess ISR with optical coherence tomography (OCT) and histopathology, comparing incidence and vascular response between stent types. Twelve adult male Bama miniature pigs underwent carotid stenting with either open-loop or closed-loop stents. The animals received antiplatelet therapy pre- and postimplantation. Postimplantation evaluations at 90days included carotid digital subtraction angiography (DSA), OCT, histopathological examination, and electron microscopy. Both stent types showed ISR as detected by OCT and DSA. OCT revealed comparable neointimal proliferation within stent struts for both types, with no significant differences in stent, lumen, and neointimal dimensions. Histopathological analysis and electron microscopy provided insights into tissue responses and healing processes following stent implantation. No significant difference in ISR incidence was found between the stent types based on a χ2 test (p=.110). OCT and hematoxylin-eosin staining exhibit the highest consistency in evaluating neointimal area. The novel porcine ISR model demonstrated similar ISR outcomes for open-loop and closed-loop stents. OCT proved to be a highly consistent and valuable tool for evaluating stent and arterial conditions, comparable to histopathological findings. However, due to a small sample size, the validity of these preliminary findings requires further investigation to be confirmed.

The impact of root end filling material type and the application of bone graft on healing of periapical tissues after endodontic microsurgery (a clinical randomized controlled trial)

To evaluate the effect of combining different bioactive root-end filling materials with composite bone graft (xenogeneic mixed with autogenous bone fragments) on the healing process of periapical tissues after endodontic micro-surgery procedure. In this triple-blinded clinical trial, 56 patients were divided into 2 main groups (28 each) according to the root-end filling material and 2 subgroups according to the presence or absence of the composite bone graft material. Group I: MTA root-end filling (n = 28) in which there are Sub-group A: without bone graft (n = 14) and Sub-group B: with composite bone graft (n = 14). Group II: TotalFill root-end filling (n = 28) in which there are Sub-group A: without bone graft (n = 14) and Sub-group B: with composite bone graft (n = 14). Healthy patients whose ages range from 20 to 50 years with small-to-medium size radiolucency in CBCT related to single-rooted maxillary teeth were included in this study. Patients were assigned a number starting from 1 to 56 and were randomly allocated to four test groups (2 main groups and 2 sub-groups) following simple randomization procedure guidelines described by IBM SPSS V23 (IBM USA) statistical analysis software. This trial was triple-blind where the patient, the outcome assessors, and the main operator were blinded to the applied intervention. Every patient was evaluated clinically and by CBCT at two main observation periods: presurgical and 12-month post-operative. They were also examined and evaluated clinically and radiographically through periapical x-rays after one week, three, and six months. Statistical analysis was performed with IBM SPSS Statistics for Windows Version 23.0. Armonk, NY: IBM Corp. Of the 56 patients enrolled in the study, 49 patients were available for the final analysis. All groups showed no statistically significant differences with regard to healing or success rates at the 12-month follow-up mark. No adverse effects were encountered. Results showed that high success rates were achieved using MTA and TotalFill in the healing of periapical lesions after endodontic surgery. The addition of bone graft in small-to-medium size lesions did not affect the success rate of endodontic surgeries.

Three-dimensional anisotropic unified continuum model for simulating the healing of damaged soft biological tissues.

The soft biological tissues have the ability to heal and self-repair after damage or injury. During the healing process, damaged tissues are replaced by newly produced undamaged tissue to restore homeostasis. Computational modeling serves as an effective tool for simulating the healing process and understanding the underlying mechanisms. In previous work, we developed the first unified continuum damage model for the healing of soft biological tissues. However, the initial theory lacked generalizability to more realistic scenarios and applicability to biomechanical problems due to the simplicity of the isotropic constitutive model and two-dimensional simulations. Therefore, we further improve our approach by developing a three-dimensional anisotropic unified healing model to address more realistic challenges. By using the Holzapfel-Gasser-Ogden model as the hyperelastic term, the influence of the collagen fibers is considered and the reorientation of fibers in healing is simulated. Three numerical examples related to hypertension, aneurysm, and restenosis of the atherosclerotic artery after balloon angioplasty are presented to demonstrate the effectiveness of the proposed model. By comparing numerical solutions and reference solutions, we demonstrate the ability of the proposed model in simulating long-term tissue healing process and analyze the impact of anisotropic terms.

Electrically-stimulated cellular and tissue events are coordinated through ion channel-mediated calcium influx and chromatin modifications across the cytosol-nucleus space

Electrical stimulation (ES) through biomaterials and devices has been implicated in activating diverse cell behaviors while facilitating tissue healing process. Despite its significance in modulating biological events, the mechanisms governing ES-activated cellular phenomena remain largely elusive. Here, we demonstrated that millisecond-pulsed temporal ES profoundly impacted a spectrum of cellular events across the membrane-cytosol-nuclear space. These include activated ion channels, intracellular calcium influx, actomyosin contractility, cell migration and proliferation, and secretome release. Such events were coordinated mainly through ES-activated ion channels and calcium oscillation dynamics. Notably, ES increased the chromatin accessibility of genes, particularly those associated with the ES-activated cellular events, underscoring the significance of epigenetic changes in ES-induced behavioral outcomes. We identified histone acetylation (mediated by histone acetyltransferases), among other chromatin modifications, is key in reshaping the chromatin landscape upon ES. These observations were further validated through experiments involving ex vivo skin tissue samples, including activated ion channels and calcium influx, increased cell proliferation and actomyosin contractility, elevated secretome profile, and more accessible chromatin structure following ES. This work provides novel insights into the mechanisms underlying ES-activated cell and tissue events, ultimately guiding design principles for the development of electrical devices and materials effective for tissue repair and wound healing.

Introduction and overview on autogenous Platelet concentrates.

This special issue on autologous platelet concentrates (APCs) provides clinicians with an overview on the current understanding of the use of these biomaterials for soft and hard-tissue regeneration. The included papers summarize scientific evidence and the clinical findings, presented in simple tables that outline potential benefits including Patient Reported Outcome Measures (PROMs). This approach enables clinicians to assess clinical relevance and researchers to identify significant gaps in the literature. The first part provides a comprehensive summary of the basic science surrounding APC, with particular focus on their preparation methods. Clear recommendations are outlined, which are crucial for obtaining high-quality APCs, alongside an exploration of how APCs may influence both soft and hard tissue healing processes. Part 2 delves into the clinical evidence for the potential benefits of APCs across a range of applications: alveolar ridge preservation, sinus floor elevation, periodontal plastic surgery, guided tissue regeneration, guided bone regeneration, the healing of Medication-Related Osteonecrosis of the Jaw (MRONJ), and endodontic surgery. In the part 3, the discussion turns to the effects of APCs on the healing of extra-oral wounds, including diabetic foot ulcers, venous leg ulcers, pressure injuries, burns, and more. For those clinicians persuaded by the evidence, the fourth section offers a detailed, step-by-step flowchart for each treatment modality, providing a clear guide for clinical application.

Healing Diabetic Foot Ulcers: A Comparative Review of Debridement Approaches

Introduction and objective: More than 400 million people worldwide suffer from diabetes today. As a result of complications of this disease, diabetic foot ulcers (DFU) develop. Wound treatment consists mainly in cleansing and stimulating tissue healing processes. Depending on the method used, this process may be shorter or longer. Review methods: In March 2023, articles found in the Medline (Pubmed) and Google Scholar databases were selected by using the following keywords: diabetic foot treatment, diabetic foot ulcers (DFU), autolytic debridement, healing DFU. Brief description of the state of knowledge: Each of the methods described in this article has its advantages and disadvantages. Surgical debridement is used in wounds with a large amount of necrotic tissue, but it can be associated with great discomfort for the patient. Clostridial collagenase ointment has been found to be effective in reducing wound area and promoting wound closure but is more expensive. The use of autolytic debridement and larval therapy is associated with a reduction in pro-inflammatory markers, while the use of moist dressings provides a suitable environment for tissue regeneration. Summary: The choice of the appropriate method depends on many factors such as: the patient's condition, the availability of materials and financial resources. This review paper provides a comprehensive overview of the benefits and drawbacks of different debridement methods for diabetic foot ulcers.

Heterojunction functionalized sodium alginate/carboxylated cellulose nanocrystals film enhancing sterilization performance for wound healing

In the realm of natural polysaccharides, hydrogen bonding is a prevalent feature, yet its role in enhancing photocatalytic antimicrobial properties has been underexplored. In this paper, heterojunctions formed by graphene oxide (GO) and ZIF-8 were locked in sodium alginate/ carboxylated cellulose nanocrystals via hydrogen bonding networks, designated as SCGZ. The SCGZ films exhibit superior photocatalytic performance compared to either ZIF-8 or heterojunctions. This enhancement is primarily due to two key factors: firstly, the hydrogen bonding network significantly enhances the transfer of protons and holes, thereby improving the separation efficiency of photo-generated carriers; secondly, the hydrogen bonding between the layers facilitates a more efficient charge transfer, which expedites the movement of electrons from ZIF-8 to GO upon illumination. In vitro studies demonstrated that the SCGZ films possess remarkable antibacterial capabilities, achieving 99.75 % and 99.61 % inhibition rates against S. aureus and E. coli, respectively. In vivo animal experiments have shown that SCGZ films can significantly accelerate the healing process of damaged tissues, with a healing efficiency of up to 90.5 %. This research provides additional insights into the development of natural polysaccharide-based multi‑hydrogen bonded macromolecules with enhanced photocatalytic properties.

Neutrophils, the major players in healing after myocardial infarction

Neutrophils are a type of immune cells with controversial functions. While their role in the protection against the microbial invasion is well known, the role in controlling and monitoring the non-infection healing processes of the injured tissue and organs are now to be discovered. Particularly in the healing after myocardial infarction, the neutrophils were considered for a long time the “bad guys”, sustaining the inflammation and interfering with the repair processes. However, all the attempt to deplete or massively inhibit their activity in experimental conditions or clinical settings lead to catastrophic results, with defective scar formation and worsening of the heart function. As recent studies pointed out the essential role of the neutrophils in monitoring and guiding all the processes involved in the proper tissular healing, a detailed investigation of mechanistic inside is required for a selective and effective design of therapeutical strategies targeting neutrophils to preserve and improve heart function after an acute myocardial infarction.

Macrophage fate: to kill or not to kill?

Macrophages are dynamic innate immune cells that either reside in tissue, serving as sentinels, or recruited as monocytes from bone marrow into inflamed and infected tissue. In response to cues in the tissue microenvironment (TME), macrophages polarize on a continuum toward M1 or M2 with diverse roles in progression and resolution of disease. M1-like macrophages exhibit proinflammatory functions with antimicrobial and anti-tumorigenic activities, while M2-like macrophages have anti-inflammatory functions that generally resolve inflammatory responses and orchestrate a tissue healing process. Given these opposite phenotypes, proper spatiotemporal coordination of macrophage polarization in response to cues within the TME is critical to effectively resolve infectious disease and regulate wound healing. However, if this spatiotemporal coordination becomes disrupted due to persistent infection or dysregulated coagulation, macrophages' inappropriate response to these cues will result in the development of diseases with clinically unfavorable outcomes. Since plasticity and heterogeneity are hallmarks of macrophages, they are attractive targets for therapies to reprogram toward specific phenotypes that could resolve disease and favor clinical prognosis. In this review, we discuss how basic science studies have elucidated macrophage polarization mechanisms in TMEs during infections and inflammation, particularly coagulation. Therefore, understanding the dynamics of macrophage polarization within TMEs in diseases is important in further development of targeted therapies.

The effect of an antioxidant gel compared to chlorhexidine during the soft tissue healing process: An animal study.

Prolonged inflammation and oxidative stress can impede healing. To enhance healing efficiency, many solutions have been employed. This is an in vivo study comparing chlorhexidine (CHX) to a commercial antioxidant gel (AO). Envelope flaps were created in the lower incisor gingival region of 60 Sprague-Dawley rats, and acellular dermal matrix (ADM) was inserted. Animals were randomly assigned to postsurgical treatment application of AO gel or 0.12% CHX twice daily. A control group received no postsurgical treatment. Data collected (before surgery, 24 h, and 72 h) included surgical images, tissue samples, and weights. Blinded scorers assessed images using a wound healing scale. Real-time polymerase chain reaction (RT-PCR) was used for gene expression of tumor necrosis factor-alpha (TNFα), interleukin-1 (IL-1), myeloperoxidase (MPO), and superoxide dismutase (SOD). The AO group scored higher than the CHX and control groups in clinical evaluation (p<0.05). At 24h, TNFα expression was upregulated in the AO group compared to CHX (p=0.027) and controls (p=0.018). The AO group had significantly higher expression of antioxidant enzyme (SOD) at 24h compared to CHX (p=0.021). All animals lost weight in the first 24h. Animals treated with AO or CHX regained more weight at 72h than control animals (p=0.034 and 0.003, respectively). Animals treated with AO healed faster. AO led to earlier upregulation of TNFα and antioxidant enzyme SOD. We hypothesized that AO promoted an earlier inflammatory process while counteracting oxidative stress by increasing antioxidant responses via SOD.

Highly efficient prevention of radiation dermatitis using a PEGylated superoxide dismutase dissolving microneedle patch

PEGylated superoxide dismutase (PEG-SOD) is commonly used as a cytoprotective agent in radiotherapy. However, its effectiveness in preventing radiation dermatitis is limited owing to its poor skin permeability. To address this issue, a PEG-SOD-loaded dissolving microneedle (PSMN) patch was developed to effectively prevent radiation dermatitis. Initially, PSMN patches were fabricated using a template mold method with polyvinylpyrrolidone K90 as the matrix material. PSMNs exhibited a conical shape with adequate mechanical strength to penetrate the stratum corneum. More than 90 % of PEG-SOD was released from the PSMN patches within 30 min. Notably, the PSMN patches showed a significantly higher drug skin permeation than the PEG-SOD solutions, with a 500-fold increase. In silico simulations and experiments on skin pharmacokinetics confirmed that PSMN patches enhanced drug permeation and skin absorption, in contrast to PEG-SOD solutions. More importantly, PSMN patches efficiently mitigated ionizing radiation-induced skin damage, accelerated the healing process of radiation-affected skin tissues, and exhibited highly effective radioprotective activity for DNA in the skin tissue. Therefore, PSMN patches are promising topical remedy for the prevention of radiation dermatitis.

Microenvironment‐Adaptive Metallo‐Polymeric Nanodecoys via Subcomponent Coordination for Bacterial Biofilm Eradication and Immunomodulation

AbstractBiofilm‐associated infections pose complex challenges that require addressing the multifaceted requirements of biofilm disruption, bacterial killing, and immunomodulation. In this study, microenvironment‐adaptive metallo‐polymeric nanodecoys (MPNs) are synthesized through one‐pot subcomponent coordination in aqueous solution, effectively eradicating bacterial biofilms and modulating immune response. Within the acidic microenvironment of biofilms, the positively charged MPNs demonstrated the ability to interact with and eliminate bacteria while facilitating a Fenton‐like reaction for efficient eradication of bacterial biofilms. As the local microenvironment shifted from a neutral to a basic state during subsequent tissue healing processes, the MPNs adaptively harness the multiple properties to bind pathogen‐associated molecular patterns, scavenge reactive oxygen species, thereby modulating the immune response, alleviating inflammation, and promoting tissue healing. This study presents an efficient strategy for preparing enzyme‐mimicking materials that closely resemble natural metalloenzymes, and the MPNs offer an efficient alternative to current antibiotic treatments for biofilm‐associated infections.

EFFECTS OF PROLOTHERAPY WITH HYPERTONIC DEXTROSE IN PATIENTS WITH KNEE OSTEOARTHRITIS: A RANDOMIZED CLINICAL TRIAL

Background: The role of prolotherapy in the healing process of damaged tissues has been confirmed in patients with degenerative joint disease. Hypertonic dextrose has been introduced as the most common solution in prolotherapy for reducing pain and improving mobility in people with knee osteoarthritis (KOA). This study aimed to compare the KOA patients undergoing hypertonic dextrose prolotherapy (DPT) with the placebo in terms of pain intensity and functional level. Methods: This triple-blind study randomized clinical trial (RCT) was conducted on patients with mild to moderate KOA who were referred to the Rheumatic Diseases Research Center (RDRC), Mashhad University of Medical Sciences, Mashhad, Iran, in the year 2021. Patients were randomly assigned to two groups of the DPT ([Formula: see text] = 47) and normal saline placebo prolotherapy ([Formula: see text] = 50) intra- and peri-articular knee joints. Treatment was monthly for three months. Western Ontario and McMaster Universities’ Arthritis Index (WOMAC) and Anterior Knee Pain Scale (AKPS) were completed before and after intervention (weeks 0, 4, 8, 12, and 16). The variables were compared between the two study groups at a significance level of less than 0.05 ([Formula: see text] &lt; 0.05). Results: The WOMAC score improved significantly compared to the baseline in both groups ([Formula: see text] &lt; 0.005). An increase in WOMAC score (the last follow-up compared to baseline) was 97.4% and 85.7% in DPT and placebo groups, respectively ([Formula: see text] = 0.06). Before the intervention and also after the first injection, the AKPS score in the normal saline group was significantly better than the dextrose group ([Formula: see text] = 0.03). The AKPS score did not differ significantly between the two groups ([Formula: see text] &gt; 0.05) in the next two visits and two-month follow-ups. Improvement of AKPS score in the last follow-up compared to baseline was reported in 66.7% and 68.4% of patients in the normal saline group and dextrose group, respectively, ([Formula: see text] = 0.86). Conclusion: Prolotherapy as intra- and peri-articular injections of hypertonic dextrose could be used to relieve pain and improve functional status in patients with mild to moderate KOA as much as a placebo does. Although no remarkable difference was observed between dextrose and placebo in the outcomes, the rate of improvement (last follow-up compared to the baseline) was relatively higher in the dextrose group than in the normal saline group.

Combined effect of pantoprazole and mesenchymal stem cells on experimentally induced gastric ulcer: implication of oxidative stress, inflammation and apoptosis pathways

Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO. Markers of oxidative stress, inflammation and apoptosis were assessed. The current data indicated that PANTO-, ADSCs- and ADSCs + PANTO-treated groups showed significant drop (p < 0.05) in serum advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEPs) along with significant elevation (p < 0.05) in serum TAC versus the untreated GU group. Moreover, the treated groups (PANTO, ADSCs and ADSCs + PANTO) displayed significant down-regulation (p < 0.05) in gastric nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase 9 (MMP-9) and caspase-3 along with significant up-regulation (p < 0.05) in vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma (PPARγ) genes expression compared to the untreated GU group. Immunohistochemical examination of gastric tissue for transforming growth factor β1 (TGF-β1), epidermal growth factor (EGF) and proliferating cell nuclear antigen (PCNA) showed moderate to mild and weak immune reactions, respectively in the PANTO-, ADSCs- and ADSCs + PANTO-treated rat. Histopathological investigation of gastric tissue revealed moderate to slight histopathological alterations and almost normal histological features of the epithelial cells, gastric mucosal layer, muscularis mucosa and submucosa in PANTO-, ADSCs- and ADSCs + PANTO-treated rats, respectively. Conclusively, the co-treatment with ADSCs and PANTO evidenced sententious physiological protection against GU by suppressing oxidative stress, inhibiting inflammation and reducing apoptosis with consequent acceleration of gastric tissue healing process.

Effectiveness of low-intensity pulsed ultrasound on osteoarthritis: molecular mechanism and tissue engineering.

Osteoarthritis (OA) is distinguished by pathological alterations in the synovial membrane, articular cartilage, and subchondral bone, resulting in physical symptoms such as pain, deformity, and impaired mobility. Numerous research studies have validated the effectiveness of low-intensity pulsed ultrasound (LIPUS) in OA treatment. The periodic mechanical waves generated by LIPUS can mitigate cellular ischemia and hypoxia, induce vibration and collision, produce notable thermal and non-thermal effects, alter cellular metabolism, expedite tissue repair, improve nutrient delivery, and accelerate the healing process of damaged tissues. The efficacy and specific mechanism of LIPUS is currently under investigation. This review provides an overview of LIPUS's potential role in the treatment of OA, considering various perspectives such as the synovial membrane, cartilage, subchondral bone, and tissue engineering. It aims to facilitate interdisciplinary scientific research and further exploration of LIPUS as a complementary technique to existing methods or surgery. Ongoing research is focused on determining the optimal dosage, frequency, timing, and treatment strategy of LIPUS for OA. Additional research is required to clarify the precise mechanism of action and potential impacts on cellular, animal, and human systems prior to its integration into therapeutic applications.

Smart polyurethane endosponges for endoluminal vacuum therapy: Integration of a bacteria sensor

The development of smart biomedical devices as efficient tools in early diagnosis and therapy monitoring has recently witnessed unprecedented growth, becoming an emerging field in biomedical engineering. Sponges for endoluminal vacuum therapy, which are intended for transmitting negative pressure as trigger for tissue regeneration and for draining infections in anastomotic leakages, are massively used implants with very complex geometry and high risk of infection. In this work, commercial polyurethane (PU) sponges have been converted into smart biomedical devices by incorporating an electrochemical sensor to monitor the growth of bacteria. Such innovative approach, which allows to track the tissue healing process avoiding further infection development, has been performed applying a three-step process: 1) activation of PU using low pressure oxygen plasma; 2) incorporation of conducting polymer (CP) nanoparticles (NPs) at the surface of the activated PU by chemical oxidative polymerization; and 3) formation of a homogeneous electroactive coating using the CP NPs obtained in 2), as growth nuclei in an electrochemical polymerization. The functionalized PU sponge is able to monitor the bacteria growth in the surrounding media by detecting the concentration of nicotinamide adenine dinucleotide (NADH) from respiration reactions in the cytosol (i.e. bacteria do not have mitochondria). Conversely, respiration in normal eukaryotic cells takes place in the mitochondria, whose double membrane is not permeable to NADH. The sensing performance of the CP-coated PU sponges (limit of detection: 0.06 mM; sensitivity: 1.21 mA/cm2) has been determined in the lab using NADH solutions, while a proof of concept have been conducted using Escherichia coli bacteria cultures.

Pulsed Electromagnetic Field Stimulation in Bone Healing and Joint Preservation: A Narrative Review of the Literature

Background: Biophysical stimulation therapy, Pulsed Electromagnetic Fields (PEMFs) and Capacitively Coupled Electric Fields (CCEFs) have significantly increased in the last twenty years. Due to this, it is necessary to have clear information regarding their efficacy, therapeutic indications and expected objectives. Application fields: There is a unanimous opinion regarding the usefulness of applying biophysical therapy on the bone compartment both in terms of the tissue-healing process and the symptoms associated with this situation. Differently, but no less important, positive results were observed in the joint compartment, especially with regard to the inhibition of the inflammatory process. Good results for chondroprotection were obtained in vitro and after a surgical procedure. New studies have shown the effectiveness also in cases of osteoporosis. Conclusions: The effectiveness of PEMFs and CCEFs on the bone-healing process and on joint preservation in the orthopedic and traumatology fields has consolidated evidence in the literature. We have also found positive results for symptoms and patient compliance with rehabilitation therapies. Therefore, their notable applications can be envisaged in the fields of prosthetic surgery and sports medicine.

DOP56 Fibrosis-related transcriptome unveils a distinctive matrix remodelling pattern in penetrating but not in stricturing ileal Crohn's Disease

Abstract Background Fibrosis underlies most of CD complications requiring surgery, such as intestinal strictures and penetrating events. We previously demonstrated there were no histopathological differences on transmural fibrosis and fibromuscular changesbetween penetrating and stricturing ileal CD. This study aimed to investigate and compare the fibrosis-related transcriptomic profiles of penetrating and stricturing ileal CD. Methods Using Nanostring technology and comparative bioinformatics, we analysed the expression of 787 genes covering the core pathways and processes involved in fibrosis, in 34 ileal surgical specimens, 11 B2 and 23 B3, the latter encompassing 12 with associated stricture(s) (B3s) and 11 without (B3o). Each patients’ tissue was retrieved from three FFPE 20mm-sections. Quality control of extracted RNA was performed according to Nanostring parameters and principal component analysis (PCA) graph for the distribution analysis. For the selection of the differentially expressed genes (DEGs) we adopted a P-adjusted &amp;lt;0.05 and a Fold Change ≤-1.5 or ≥ 1.5. Statistical analysis adopted level of significance at 5%. Results We included 34 patients, in a well-balanced sample for age (at diagnosis and at surgery), gender, CD localization, perianal disease and therapy. Inflammation and fibrosis histopathological scoring were similar (median of 3 and 1, respectively), in the three groups. No DEGs differentiated B3s and B3o subgroups, which were grouped as B3. The B2 and B3 groups showed a very good clustering on the gene heatmap, which uncovered 30 DEGs between the 2 groups, all being upregulated in B3 and, conversely, downregulated in B2 patients – Figure. More than half of the upregulated genes have been established or partially involved in CD fibrogenesis (yellow-box and line, respectively), while 8 DEGs have been implicated in fibrosis in other organs (brown-line box) and 3 others having an anti-fibrotic role in other tissues (green-line box). Importantly, the vast majority of the most significantly active biologic processes and pathways in the B3 group were related to response to TGF b and matrix organization, production and degradation, unveiling a continuous process of tissue healing and destruction distinctive of this aggressive phenotype. Conclusion Despite the histopathological similarities of fibrosis between stricturing and penetrating ileal CD, their fibrosis-related transcriptomic profiles are distinct. Penetrating CD was remarkable for the activation of all the unveiled DEGs and of biologic pathways concerning permanent matrix production and degradation. Hence, although fibrosis underlies both penetrating and stricturing CD, therapeutic targets may differ even in end-of-stage disease.

CaO2-Cu2O micromotors accelerate infected wound healing through antibacterial functions, hemostasis, improved cell migration, and inflammatory regulation.

During the wound tissue healing process, the relatively weak driving forces of tissue barriers and concentration gradients lead to a slow and inefficient penetration of bioactive substances into the wound area, consequently showing an impact on the effectiveness of deep wound healing. To overcome these challenges, we constructed biocompatible CaO2-Cu2O "micromotors". These micromotors reacted with the fluids at the wound site, releasing oxygen bubbles and propelling particles deep into the wound tissue. In vitro experimental results revealed that these micromotors not only exhibited antibacterial and hemostatic functions but also facilitated the migration of dermal fibroblasts and vascular endothelial cells, while modulating the inflammatory microenvironment. A methicillin-resistant Staphylococcus aureus infected full-thickness-wound model was created in rats, in which CaO2-Cu2O micromotors markedly expedited the wound healing process. Specifically, CaO2-Cu2O provided a sterile microenvironment for wounds and increased the amounts of M1-type macrophages during infection and inflammation. During the proliferation and remodeling stages, the amount of M1 macrophages gradually decreased, while the amount of M2 macrophages increased, and CaO2-Cu2O did not prolong the inflammatory period. Furthermore, the introduction of a regenerated silk fibroin (RSF) film on the wound surface successfully enhanced the therapeutic effects of CaO2-Cu2O against the infected wound. The combined application of oxygen-producing CaO2-Cu2O micromotors and a RSF film demonstrates significant therapeutic potential and emerges as a promising candidate for the treatment of infected wounds.

Combination of Platelet-rich Fibrin (PRF) in Advanced Periodontitis Stage Treatment

Introduction: The treatment of advanced periodontitis has been a challenge for clinicians. Platelet-rich fibrin (PRF) is a second-generation platelet concentrate that contains various growth factorss and cytokines that promote tissue regeneration. The use of PRF in combination with other regenerative materials and techniques has been shown to be effective in the treatment of intrabony defects. This case series aims to evaluate the efficacy of PRF combinations in the regenerative treatment of patients with advanced periodontitis. Case report: Two patients diagnosed with advanced periodontitis (stage III/IV grade C) were selected for this study. After the completion of periodontal initial therapy, there were still pockets with a probing depth ≥ 5 mm (5–10 mm). Therefore, surgical interventions were planned. The first case used the combination of PRF with bone graft and guided tissue regeneration (GTR), while open flap debridement (OFD) with the addition of PRF and bone graft to create sticky bone was done in the second case. Three to five months of follow-up showed favorable outcomes, as evidenced by reductions in probing depth (PD), gains in clinical attachment level, and filling of bone defects, as well as improvements in patient comfort and rapid wound healing. Conclusion: The combination of PRF with grafting material and/or GTR has been shown to be a beneficial therapeutic approach for periodontal regenerative therapy. Platelet-rich fibrin in periodontal surgery may accelerate the tissue healing process.